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Persistent Staphylococcus aureus isolates from two independent cases of bacteremia display increased bacterial fitness and novel immune evasion phenotypes.

Richards RL, Haigh RD, Pascoe B, Sheppard SK, Price F, Jenkins D, Rajakumar K, Morrissey JA - Infect. Immun. (2015)

Bottom Line: Several novel traits were associated specifically with both independent sets of persistent S. aureus isolates compared to both the initial isolates and the isolates from resolved infections (resolved isolates).These traits included (i) increased growth under nutrient-poor conditions; (ii) increased tolerance of iron toxicity; (iii) higher expression of cell surface proteins involved in immune evasion and stress responses; and (iv) attenuated virulence in a Galleria mellonella larva infection model that was not associated with small-colony variation or metabolic dormancy such as had been seen previously.Overall, our data indicate a novel role for MprF function during development of S. aureus persistence by increasing bacterial fitness and immune evasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Infection, Immunity of Inflammation, University of Leicester, Leicester, United Kingdom.

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Related in: MedlinePlus

A diagrammatical representation of PB1 (A) and PB3 (B) treatment timelines. Time points for each blood culture collection and periods of antibiotic prescription are indicated relative to the initial positive blood culture for each bacteremia case. +BC, positive blood culture; −BC, negative blood culture; Co-Amoxiclav, amoxicillin-clavulanic acid.
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Figure 1: A diagrammatical representation of PB1 (A) and PB3 (B) treatment timelines. Time points for each blood culture collection and periods of antibiotic prescription are indicated relative to the initial positive blood culture for each bacteremia case. +BC, positive blood culture; −BC, negative blood culture; Co-Amoxiclav, amoxicillin-clavulanic acid.

Mentions: To investigate the genetic and phenotypic traits specifically associated with S. aureus persistence, multiple temporal isolates were sampled from two patients admitted to the University Hospitals of Leicester between 2009 and 2010 who had been diagnosed with persistent MRSA bacteremia (infection cases designated PB1 and PB3). Three additional patients were diagnosed with resolved MRSA bacteremia (RB1, RB4, and RB5); i.e., the infections were treated successfully. Individual infection timelines were produced (Fig. 1), and relevant clinical information was recorded (Table 1). Two individual positive blood cultures were collected on day 15 and day 32, respectively, for both PB1 and PB3; this allowed the confirmation of homogenous blood-borne bacterial populations in those cases at those time points. PB1 was diagnosed with infective endocarditis following transthoracic echocardiography (TTE) on day 6, which offers a potential source for the persistent and, ultimately, fatal infection in this case. In contrast, the MRSA bacteremia in PB3 was diagnosed as a secondary infection associated with an ulcer in an infected foot, which was amputated on day 20, thereby eliminating the only identified focus of infection prior to the subsequent positive blood cultures (day 29 onward). On day 76 following the first positive blood culture, a spinal abscess and osteomyelitis were suspected, providing alternative possible infective foci in PB3. All MRSA bacteremia isolates, independently of infection type (persistent or resolved bacteremia), belonged to sequence type 22 (ST22) and agr type I and exhibited a staphylococcal cassette chromosome mec (SCCmec) type IVh element (31–34), indicating that these isolates were derivatives of Epidemic MRSA-15 (EMRSA-15). Whole-genome analysis revealed clustering of isolates as determined on the basis of homologous sequence variation at shared core genes (Fig. 2).


Persistent Staphylococcus aureus isolates from two independent cases of bacteremia display increased bacterial fitness and novel immune evasion phenotypes.

Richards RL, Haigh RD, Pascoe B, Sheppard SK, Price F, Jenkins D, Rajakumar K, Morrissey JA - Infect. Immun. (2015)

A diagrammatical representation of PB1 (A) and PB3 (B) treatment timelines. Time points for each blood culture collection and periods of antibiotic prescription are indicated relative to the initial positive blood culture for each bacteremia case. +BC, positive blood culture; −BC, negative blood culture; Co-Amoxiclav, amoxicillin-clavulanic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496624&req=5

Figure 1: A diagrammatical representation of PB1 (A) and PB3 (B) treatment timelines. Time points for each blood culture collection and periods of antibiotic prescription are indicated relative to the initial positive blood culture for each bacteremia case. +BC, positive blood culture; −BC, negative blood culture; Co-Amoxiclav, amoxicillin-clavulanic acid.
Mentions: To investigate the genetic and phenotypic traits specifically associated with S. aureus persistence, multiple temporal isolates were sampled from two patients admitted to the University Hospitals of Leicester between 2009 and 2010 who had been diagnosed with persistent MRSA bacteremia (infection cases designated PB1 and PB3). Three additional patients were diagnosed with resolved MRSA bacteremia (RB1, RB4, and RB5); i.e., the infections were treated successfully. Individual infection timelines were produced (Fig. 1), and relevant clinical information was recorded (Table 1). Two individual positive blood cultures were collected on day 15 and day 32, respectively, for both PB1 and PB3; this allowed the confirmation of homogenous blood-borne bacterial populations in those cases at those time points. PB1 was diagnosed with infective endocarditis following transthoracic echocardiography (TTE) on day 6, which offers a potential source for the persistent and, ultimately, fatal infection in this case. In contrast, the MRSA bacteremia in PB3 was diagnosed as a secondary infection associated with an ulcer in an infected foot, which was amputated on day 20, thereby eliminating the only identified focus of infection prior to the subsequent positive blood cultures (day 29 onward). On day 76 following the first positive blood culture, a spinal abscess and osteomyelitis were suspected, providing alternative possible infective foci in PB3. All MRSA bacteremia isolates, independently of infection type (persistent or resolved bacteremia), belonged to sequence type 22 (ST22) and agr type I and exhibited a staphylococcal cassette chromosome mec (SCCmec) type IVh element (31–34), indicating that these isolates were derivatives of Epidemic MRSA-15 (EMRSA-15). Whole-genome analysis revealed clustering of isolates as determined on the basis of homologous sequence variation at shared core genes (Fig. 2).

Bottom Line: Several novel traits were associated specifically with both independent sets of persistent S. aureus isolates compared to both the initial isolates and the isolates from resolved infections (resolved isolates).These traits included (i) increased growth under nutrient-poor conditions; (ii) increased tolerance of iron toxicity; (iii) higher expression of cell surface proteins involved in immune evasion and stress responses; and (iv) attenuated virulence in a Galleria mellonella larva infection model that was not associated with small-colony variation or metabolic dormancy such as had been seen previously.Overall, our data indicate a novel role for MprF function during development of S. aureus persistence by increasing bacterial fitness and immune evasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Infection, Immunity of Inflammation, University of Leicester, Leicester, United Kingdom.

Show MeSH
Related in: MedlinePlus